The long-term goal of the research program has been to understand "stress"--what is it, what modulates it, and how it impacts different levels of organismic functioning. All of the seemingly diverse work of the PI's laboratory flows from this fundamental interest. The PI's early work was behavioral. He gradually shifted to an interest in neural mechanisms, and more recently has added work on endocrine and immune consequences of exposure to stressors. He now studies behavioral, neurochemical, neuroendocrine, and immune changes induced by stressors with the long-term goal of understanding how these different levels communicate, interact, determine, and modulate each other. There are numerous studies of stress at each of these levels of function, but relatively few multidisciplinary efforts to understand how the levels are integrated. His long-term goal is to arrive at such an integrated understanding. The specific work of the next 5 years will focus on 3 major issues: 1) neural, endocrine, and immune mechanisms by which stressors modulate in vivo immune function; 2) the role of peripheral vagus nerve in mediating cytokine-to-brain communication; 3) the neural mechanisms which mediate the behavioral consequences of stressors; and 4) the role of central nervous system cytokines in integrating these phenomena.